Association between the P12A and cl431t polymorphisms in the peroxisome proliferator activated receptor gamma (PPAR gamma) gene and type 2 diabetes

Variation in the peroxisome proliferator-activated receptor gamma, (PPAR ga mma) gene may play a role in the development of type 2 diabetes mellitus. T herefore we investigated the association between the P12A and c1431t polymo rphisms in the PPAR gamma gene and type 2 diabetes. The incidence of the P1 2A polymorphism was determined by PCR-RFLP and the c1431t by single-strand conformation polymorphism analysis in 219 patients with, and 429 without ty pe 2 diabetes. The frequency of the A allele of P12A polymorphism was 0.16 and the t allele of c1431t polymorphism, 0.13 in patients with type 2 diabe tes, and 0.13 and 0.12 respectively in subjects without diabetes. 3.2% of p atients with and 1.4% without type 2 diabetes were A12A. Since the polymorp hisms are not linked the association of the 9 possible genotypes with type 2 diabetes was determined. All patients with genotype A12A/c1431c had type 2 diabetes (n=3, p=0.038). There was no association between A12A/t1431t and diabetes. DNA sequencing revealed no additional mutations in the coding re gion of the PPAR gamma gene in genotypes A12A/c1431c or A12A/t1431t. The as sociations found between polymorphisms in the PPAR gamma, gene and type 2 d iabetes suggest that either the A12 isoform is functional leading to a pred isposition to type 2 diabetes in homozygotes or that there is a third, unkn own mutation linked to the A12/c1431 haplotype which is responsible.